Pharmacokinetics of metoclopramide in goats

The pharmacokinetics of a parenteral formulation of metoclopramide (monochloride monohydrate) were determined following single intravenous (i.v.) and intramuscular (i.m.) 0.5-mg/kg doses to two groups of 4 goats in a crossover design. Mean serum concentrations of metoclopramide following i.v. administration of 0.5 mg/kg declined rapidly from a peak of 277.5 ng/ml at 3 min post-dosing to 25 ng/ml at 90 min. Serum concentrations were not detectable by 120 min after drug administration. The curve of serum concentrations vs. time was characteristic of a two-compartment open model. Mean parameters from analysis of the individual i.v. data gave a biological half-life of 0.62 h and a volume of distribution of the central compartment of 1.34 l/kg. Serum concentrations of metoclopramide following i.m. administration of 0.5 mg/kg rose rapidly to a peak of 160.9 ng/ml at 15 min post-dosing and then declined in parallel with the elimination phase of the i.v. study. These data were best described by a two-compartment open model with first-order absorption. The mean biological half-life was 1.04 h. There were no adverse reactions associated with metoclopramide at the 0.5-mg/kg dose administered by either route.     

Comparative pharmacokinetics of diminazene in lactating goats and sheep

The pharmacokinetic aspects of diminazene aceturate were studied in lactating goats and sheep after single intravenous and intramuscular administrations of 3.5 mg/kg b.wt. Plasma and milk concentrations were determined by use of reversed phase high-performance liquid chromatography (HPLC) after ion-pair extraction. Following intravenous injection, the disposition of diminazene in goats and sheep conformed to a two-compartment model with rapid distribution and slower elimination phases. Values of (t1/2 beta) were obtained indicating a slower final disappearance of the drug from plasma of sheep (21.17 h) than in goats (16.39 h). Diminazene concentrations were maintained for more than 4 days in the plasma of goats and sheep. In both species of animals, diminazene was rapidly absorbed following intramuscular administration of 3.5 mg/kg b.wt. The peak plasma concentrations (Cmax) were 7.00 and 8.11 micrograms/ml and were attained at (Tmax) 0.92 and 1.12 hours in goats and sheep, respectively. The elimination half-life (t1/2el) of diminazene after intramuscular administration was shorter in goats (16.54 h) than in sheep (18.80 h). Systemic bioavailabilities (F%) of diminazene after intramuscular administration were 94.94% and 82.64% in goats and sheep, respectively. Diminazene could be detected in milk of goats and sheep within 10 min post-injection. Milk concentrations of the drug were lower in goats than in sheep and were detected for 5 and 6 days following both routes of administration, respectively.     

Comparative pharmacokinetics of oxytetracycline in rainbow trout (Salmo gairdneri) and African catfish (Clarias gariepinus)

A comparative pharmacokinetic study was conducted in rainbow trout (Salmo gairdneri) and African catfish (Clarias gariepinus) following intravenous (i.v.) and intramuscular (i.m.) administration of oxytetracycline (OTC) at a dose rate of 60 mg/kg body weight. Trout and catfish were kept in aerated tap water in tanks at constant temperatures of 12 degrees C and 25 degrees C, respectively. The two- and three-compartment open models adequately described plasma drug disposition in African catfish and rainbow trout respectively, following i.v. OTC administration. Compared to catfish (COP = 86 +/- 10 micrograms/ml) an eightfold higher extrapolated zero time concentration was obtained in trout (COP = 753 +/- 290 micrograms/ml). A significant difference was observed with respect to the relatively large apparent distribution volumes (Vd(area] after i.v. OTC administration (trout, mean value: 2.1 l/kg; catfish, mean value: 1.3 l/kg). The mean final elimination half-lives of both fish species were greater than previously reported in mammals (trout, 89.5 h; catfish, 80.3 h). A mean maximum plasma concentration (Cmax = 56.9 micrograms/ml) was obtained in trout at 4 h after i.m. administration of OTC. In catfish a lower Cmax of 43.4 micrograms/ml was determined at about 7 h. No significant difference was observed with respect to bioavailability following i.m. administration of OTC (trout, 85%; catfish, 86%).     

Disposition of tylosin in goats.

The disposition kinetics of tylosin was studied in goats after intravenous or intramuscular injection of 15 mg/kg b. wt. Following i.v. injection, tylosin was rapidly and widely distributed in goats (half life of distribution: 0.2 h and volume of distribution: 1.7 l/kg). It was slowly eliminated with a mean elimination half life of 3.04 h and a total body clearance rate of 6.8 ml/kg/min. Following i.m. injection, tylosin was slowly absorbed (T1/2ab of 1.82 h). Tylosin concentration in serum was greater than 1 microgram/ml after 1 h and persisted up to 12 h post-injection. The peak concentration (Cmax, 2.38 micrograms/ml) was obtained after 4.19 h. The systemic bioavailability of tylosin injected intramuscularly was 72.6% and the serum protein bound fraction was 37.6% of the total drug. Tylosin was excreted in milk and urine at concentrations much higher than that in serum. Low concentrations of tylosin were reported in ruminal juice of goats. In conclusion tylosin should be injected every 15 hours to obtain an appreciable concentration in serum, milk and urine.     

Acyclovir (Zovirax®) pharmacokinetics in Quaker parakeets, Myiopsitta monachus

The pharmacokinetics of intravenous (i.v.) and intramuscular (i.m.) single-dose administration of acyclovir were determined in Quaker parakeets. After i.v. injection at a dose of 20 mg/kg of acyclovir, elimination half-life was estimated at 0.65 h, volume of distribution at steady state was 627.65 ml/kg, and clearance was 11.22 ml/kg/min. The estimated pharmacokinetic values after i.m. injection at a dose of 40 mg/kg of acyclovir were an elimination half-life of 0.71 h and a bioavailability of 90.1%. The peak plasma acyclovir concentration occurred at 15 min when the drug was administered i.m. Plasma concentrations of acyclovir were undetectable 4-6 h after i.v. administration and 6-8 h after i.m. administration. Oral (capsules) and intravenous (sodium salt) formulations of acyclovir were given by gavage at 80 mg/kg. Peak concentrations with the sodium salt formulation were lower and developed more slowly than with the capsules. In studies designed to detect excessive drug accumulation or adverse side effects, acyclovir was administered i.m. at 40 mg/kg every 8 h for 7 days. Plasma concentrations were determined 15 min after (peak) and just prior to drug administration (trough). In another study acyclovir was gavaged at a dose of 80 mg/kg every 8 h for 4 days. Acyclovir plasma concentrations were determined just prior to and 2 h after drug administration. In both experiments, the birds maintained normal appetite and weight and did not exhibit excessive drug accumulation. Acyclovir plasma concentrations ranging from 2.07 +/- 1.09 micrograms/ml to 3.93 +/- 1.13 micrograms/ml were maintained for 4 days when acyclovir was administered in the feed and water (sole source of food and water).(ABSTRACT TRUNCATED AT 250 WORDS)     

Distribution of kanamycin in ocular tissues of calves

The ocular distribution of kanamycin following intramuscular, bulbar subconjunctival injection, or after constant rate intravenous infusion to calves was studied. Steady-state plasma concentrations of kanamycin were achieved in either normal calves, or in those experimentally infected with Moraxella bovis, and the concentrations of kanamycin in the serum, aqueous humor, vitreous body, tears, and the ocular tissues were measured. Kanamycin was not detected in the retina, lens, vitreous body, or the aqueous humor of any eyes, but the concentration of drug in the tears, conjunctiva, cornea and the orbital lacrimal gland of these calves ranged between 18 and 21% of that in serum. At steady-state plasma levels, the kanamycin concentrations in tears from eyes with keratoconjunctivitis and from normal eyes were similar. A study using lyophilized, powdered, ocular tissues in vitro showed that kanamycin was highly bound to the bovine retina and iris, and could be eluted using 0.2 N NaOH. The binding of kanamycin to other ocular tissues, including cornea, conjunctiva and lens, was significantly less. The concentration of kanamycin in the serum and the tears of calves was also measured after intramuscular or bulbar subconjunctival injection. After intramuscular administration of kanamycin (10 mg/kg of body-weight), the mean serum concentration was maximal at 1 h (32 micrograms/ml) and remained greater than or equal to 1.0 microgram/ml for 8 h. The mean tear concentration was maximal (3.1 micrograms/ml) at 30 min, and remained greater than or equal to 1.5 micrograms/ml for only 2.5 h. Following bulbar subjunctival administration of kanamycin (100 mg, single subconjunctival dose), the mean tear concentration was 1127 micrograms/ml at 30 min, less than or equal to 4.1 micrograms/ml at 4 h, and thereafter was less than or equal to 1.0 microgram/ml. It was concluded that kanamycin has limited distribution to the ocular tissues following parenteral administration. Binding of the drug to the ocular pigments may be responsible for its limited intraocular penetration.     

Disposition of tylosin in goats

The disposition kinetics of tylosin was studied in goats after intravenous (i.v.) or intramuscular (i.m.) injection of 15 mg/kg body wt. Following i.v. injection, tylosin was rapidly and widely distributed with a distribution half-life of 0.2 h and volume of distribution of 1.7 l/kg. It was slowly eliminated with a mean elimination half-life of 3.04 h and a total body clearance rate of 6.8 ml/kg/min. Following i.m. injection, tylosin was slowly absorbed (tau 1/2 ab of 1.82 h). Tylosin concentration in serum was greater than 1 microgram/ml after 1 h and persisted up to 12 h post-injection. The peak concentration (Cmax 2.38 micrograms/ml) was obtained after 4.19 h. The systemic bioavailability of tylosin injected intramuscularly was 72.6% and the serum protein bound fraction was 37.59% of the total drug. Tylosin was excreted in milk and urine at concentrations much higher than that in serum. Low concentrations of tylosin were reported in ruminal juice of goats. In conclusion tylosin should be injected every 14 h to obtain an appreciable concentration in serum, milk and urine.     

Pharmacokinetics of difloxacin in goats

The pharmacokinetic properties of difloxacin following intravenous (i.v.) and intramuscular (i.m.) administration in goats were investigated. Difloxacin was administered in a single dose of 5 mg/kg body weight for both routes and was assayed in biological fluids (serum and urine) to determine its concentrations, kinetic behaviour and systemic availability. Following a single i.v. injection, the serum difloxacin level was best approximated to follow a two-compartment open model using weighted non-linear regression analysis. The elimination half-life (t1/2 beta) was 6.3 +/- 0.11 h. The volume of distribution at steady-state (Vdss) was 1.1 +/- 0.012 L/kg and the total body clearance (Cltot) was 0.13 +/- 0.001 L/kg/h. Following a single i.m. administration, difloxacin was rapidly absorbed and the mean peak serum concentration (4.1 +/- 0.23 micrograms/ml) was achieved 1 h post administration. The extent of serum protein binding of difloxacin in goats was 13.79 +/- 1.02% and the systemic availability was 95.4 +/- 1.17%. Following i.m. injection of difloxacin at a dose rate of 5 mg/kg b.wt for 5 consecutive days, the drug could not be detected in serum and urine at 4th day from the last injection.     

Body fluid and endometrial concentrations of ketoconazole in mares after intravenous injection or repeated gavage

After single oral administration of ketoconazole (30 mg/kg bodyweight [bwt]) in 50 ml of corn syrup to a healthy mare, the drug was not detected in serum. Ketoconazole in 0.2 N HC1 was administered intragastrically to six healthy adult horses in five consecutive doses of 30 mg/kg bwt at 12 h intervals. Ketoconazole concentrations were measured in serum, synovial fluid, peritoneal fluid, cerebrospinal fluid (CSF), urine and endometrium. Mean peak serum ketoconazole concentration was 3.76 micrograms/ml at 1.5 to 2 h after intragastric administration. Mean peak synovial concentration was 0.87 micrograms/ml 3 h after the fifth dose. Similarly, mean peritoneal concentration peaked 3 h after the fifth dose at 1.62 micrograms/ml. Mean endometrial concentrations peaked at 2.73 micrograms/ml 2 h after the fifth dose. Ketoconazole was detected in the CSF of only one of the six mares at a concentration of 0.28 micrograms/ml 3 h after the fifth dose. The highest measured concentration of ketoconazole in urine was 6.15 micrograms/ml 2 h after the fifth dose. A single intravenous injection of ketoconazole (10 mg/kg bwt) was given to one of the six mares; the overall elimination rate constant was estimated at 0.22/h and bioavailability after oral administration was 23 per cent.     

Pharmacokinetics, metabolism and renal clearance of flumequine in veal calves

The pharmacokinetics of flumequine was studied in 1-, 5- and 18-week-old veal calves. A two-compartment model was used to fit the plasma concentration-time curve of flumequine after the intravenous injection of 10 mg/kg of a 10% solution. The elimination half-life (t1/2 beta) of the drug ranged from 6 to 7 h. The Vd beta and ClB of 1-week-old calves (1.07 l/kg, 1.78 ml/min/kg) were significantly lower than those of 5-week-old (1.89 l/kg, 3.23 ml/min/kg) and 18-week-old calves (1.57 l/kg, 3.10 ml/min/kg). After the oral administration of 10 mg/kg of a 2% flumequine formulation mixed with milk replacer, the Cmax was highest in 1-week-old (9.27 micrograms/ml) and lowest in 18-week-old calves (4.47 micrograms/ml). The absorption was rapid (Tmax of approximately 3 h) and complete. When flumequine itself and a formulation containing 2% flumequine and 20 X 10(6) iu of colistin sulphate were mixed with milk replacer and administered at the same dose rate, absorption was incomplete and Cmax was lower. The main urinary metabolite of flumequine was the glucuronide conjugate (approximately 40% recovery within 48 h of intravenous injection) and the second most important metabolite was 7-hydroxy-flumequine (approximately 3% recovery within 12 h of intravenous injection). Only 3.2-6.5% was excreted in the urine unchanged. After oral administration a 'first-pass' effect was observed, with a significant increase in the excretion of conjugated drug. For 1-week-old calves it is recommended that the 2% formulation should be administered at a dose rate of 8 mg/kg every 24 h or 4 mg/kg every 12 h; for calves over 6 weeks old, the dose should be increased to 15 mg/kg every 24 h or 7.5 mg/kg every 12 h. The formulation containing colistin sulphate should be administered to 1-week-old calves at a flumequine dose of 12 mg/kg every 24 h or 6 mg/kg every 12 h.     

Intra-abdominal versus intramuscular application of two ampicillin preparations in cows

Plasma ampicillin concentrations were determined in a cross-over trial involving five cows after single intramuscular or intra-abdominal administration of sodium ampicillin (10 mg/kg) and ampicillin anhydrate (40 mg/kg). After injection of sodium-ampicillin, high plasma concentrations were reached within 10 min; Cmax following intramuscular injection was 9.1 micrograms/ml and after intra-abdominal injection 7.5 micrograms/ml. Urine concentrations of ampicillin were low after 24 h (1-1.5 micrograms/ml). No significant changes in blood leucocyte numbers, plasma zinc, iron or fibrinogen levels occurred. After injection of ampicillin anhydrate 1 h elapsed before maximum plasma levels were obtained; Cmax was 5.4 micrograms/ml after intramuscular and 6.7 micrograms/ml after intra-abdominal administration. Urine concentrations were very high (238-303 micrograms/ml) after 24 h and stayed above 1 microgram/ml for 6 days. After administration of ampicillin anhydrate a significant increase in blood neutrophils (P less than 0.01) and a significant increase in plasma fibrinogen was measured after intramuscular and intra-abdominal injection (P less than 0.05). A significant decrease in plasma zinc concentration after intra-abdominal injection occurred (P less than 0.05). In abdominal surgery in cows in which contamination cannot be prevented, and practical objections inhibit preoperative administration, intramuscular or intra-abdominal administration during surgery of sodium ampicillin seems justified. Ampicillin anhydrate should not be used intra-abdominally.     

Clinical pharmacokinetics of flumequine in calves

The minimal inhibitory concentration (MIC) of flumequine for 249 Salmonella, 126 Escherichia coli, and 22 Pasteurella multocida isolates recovered from clinical cases of neonatal calf diarrhoea, pneumonia and sudden death was less than or equal to 0.78 microgram/ml. The pharmacokinetics of flumequine in calves was investigated after intravenous (i.v.), intramuscular (i.m.) and oral administration. The two-compartment open model was used for the analysis of serum drug concentrations measured after rapid i.v. ('bolus') injection. The distribution half-life (t1/2 alpha) was 13 min, elimination half-life (t1/2 beta) was 2.25 h, the apparent area volume of distribution (Vd(area)), and the volume of distribution at steady state (Vd(ss)) were 1.48 and 1.43 l/kg, respectively. Flumequine was quickly and completely absorbed into the systemic circulation after i.m. administration of a soluble drug formulation; a mean peak serum drug concentration (Cmax) of 6.2 micrograms/ml was attained 30 min after treatment at 10 mg/kg and was similar to the concentration measured 30 min after an equal dose of the drug was injected i.v. On the other hand, the i.m. bioavailability of two injectable oily suspensions of the drug was 44%; both formulations failed to produce serum drug concentrations of potential clinical significance after administration at 20 mg/kg. The drug was rapidly absorbed after oral administration; the oral bioavailability ranged between 55.7% for the 5 mg/kg dose and 92.5% for the 20 mg/kg dose. Concomitant i.m. or oral administration of probenecid at 40 mg/kg did not change the Cmax of the flumequine but slightly decreased its elimination rate. Flumequine was 74.5% bound in serum. Kinetic data generated from single dose i.v., i.m. and oral drug administration were used to calculate practical dosage recommendations. Calculations showed that the soluble drug formulation should be administered i.m. at 25 mg/kg every 12 h, or alternatively at 50 mg/kg every 24 h. The drug should be administered orally at 30 and 60 mg/kg every 12 and 24 h, respectively. Very large, and in our opinion impractical, doses of flumequine formulated as oily suspension are required to produce serum drug concentrations of potential clinical value.     

Pharmacokinetics and dosage of chlorpromazine in goats

Pharmacokinetic parameters which describe the distribution and elimination of chlorpromazine in goats were determined. Following the intravenous administration of a single dose (2.5 mg/kg), disposition of the drug was described in terms of the biexponential expression C _p= Ae^-αt+ Be^-βt. Based on total (free and bound) chlorpromazine levels in plasma, pseudo-distribution equilibrium was rapidly attained, and the elimination half-life was 1.51 ± 0.48 h (mean ± SD, n = 8). Total body clearance, which is the sum of all clearance processes, was 80 ± 25 ml/min/kg. The curves of an animal representative of the group, based on individual rate constants associated with the two-compartment open model, showed that at 5 h after drug administration 8% and 6% of the dose were present in the peripheral and central compartments, respectively. The kinetic parameters of chlorpromazine determined at a dosage level of 10 mg/kg body weight in six goats showed that the drug followed first-order kinetics and kinetic parameters were similar after both dose levels. Based on these findings and therapeutic plasma levels, a satisfactory intravenous regimen should be 2.0 – 3.5 mg/kg and the drug action will persist for 5–6 h.     

Pharmacokinetics of probenecid in sheep

Six Merino ewes were given 1 g (27 g/kg) probenecid by the intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) routes. After i.v. injection, the biological half-life was 1.55 h and apparent volume of distribution at the steady state (Vdss) 0.18 l/kg. Body clearance (ClB) and renal clearance (ClR) were 0.12 l/h/kg and 0.03 l/h/kg, respectively. Approximately 28% of unchanged probenecid was excreted in urine. Plasma probenecid concentrations after i.v., i.m. and s.c. injections were 133, 37, and 31 micrograms/ml, respectively, at 15 min; 76, 36, and 34 micrograms/ml at 1 h; and 43, 23 and 34 micrograms/ml at 2 h. The average bioavailability of probenecid given by i.m. and s.c. injection was 46% and 34%, respectively. However, after 2 h, probenecid plasma concentrations remained higher when it was given subcutaneously than when it was given intramuscularly. Urine output was correlated positively (P less than 0.05) with kel and ClB. Urine pH increased significantly (P less than 0.01) for the first 2 h, and then steadily declined over the subsequent 6 h. The results suggested that probenecid in sheep was rapidly eliminated because it was rapidly excreted in the normal but alkaline urine. Subcutaneous administration of probenecid in animals may be a useful alternative to oral or i.v. administration.     

Pharmacokinetics and body fluid and endometrial concentrations of ormetoprim-sulfadimethoxine in mares.

Six healthy adult mares were each given an oral loading dose of ormetoprim(OMP)-sulfadimethoxine (SDM) at a dosage of 9.2 mg of OMP/kg and 45.8 mg of SDM/kg, followed by four maintenance doses of 4.6 mg of OMP/kg and 22.9 mg of SDM/kg, at 24 h intervals. Ormetoprim and SDM concentrations were measured in serum, synovial fluid, peritoneal fluid, cerebrospinal fluid, urine and endometrium. The highest mean serum OMP concentration was 0.92 micrograms/mL 0.5 h after the first dose; the highest mean SDM concentration was 80.9 micrograms/mL 8 h after the first dose. The highest mean synovial fluid concentrations were 0.14 microgram of OMP/mL and 28.5 micrograms of SDM/mL 12 h after the first dose. The highest mean peritoneal fluid concentrations were 0.19 micrograms of OMP/mL 6 h after the first dose and 25.5 micrograms of SDM/mL 8 h after the fifth dose. The highest mean endometrial concentrations were 0.56 micrograms of OMP/g and 28.5 micrograms of SDM/g 4 h after the fifth dose. The mean cerebrospinal fluid concentrations were 0.08 micrograms of OMP/mL and 2.1 micrograms of SDM/mL 5 h after the fifth dose. Mean trough urine drug concentrations were greater than or equal to 0.4 micrograms of OMP/mL and greater than or equal to 172 micrograms of SDM/mL. Two of the mares were each given a single intravenous (IV) injection of OMP and SDM at a dosage of 9.2 mg of OMP/kg and 45.8 mg of SDM/kg. Excitation and muscle fasciculations were observed in both mares after IV administration and all scheduled blood samples could be collected from only one of the two mares.(ABSTRACT TRUNCATED AT 250 WORDS)     

Some pharmacokinetic parameters of the trypanocidal drug homidium bromide in Friesian and Boran steers using an enzyme-linked immunosorbent assay (ELISA)

Pharmacokinetic studies on the trypanocidal drug homidium bromide using a competitive enzyme immunoassay (detection limit 0.1 ng/mL) are reported for non-infected Friesian and Boran steers following treatment with homidium bromide at a dose of 1.0 mg/kg b.w. Following intravenous (i.v.) treatment of Friesian steers (n = 5), the mean serum drug concentrations were 31.9 +/- 2.1 and 3.9 +/- 0.4 ng/mL at 1 and 24 h, respectively. The decline in serum drug concentration was tri-exponential with half-lives of 0.064 +/- 0.037 h for t1/2 alpha, 7.17 +/- 1.87 h for t1/2 beta and 106.3 +/- 6.6 h for t1/2 gamma for distribution and elimination phases 1 and 2, respectively. Drug was detectable in serum for 17 days following treatment. The mean residence time (MRT) was 63.4 +/- 7.5 h. Following intramuscular (i.m.) treatment of Friesian steers (n = 5), the drug concentration at 1 h after treatment was 72.5 +/- 2.2 ng/mL. This declined to 9.8 +/- 1.8 ng/mL at 24 h. Low concentrations of between 0.1 and 0.3 ng/mL remained in circulation for up to 90 days post-treatment. Following intramuscular treatment of Boran steers (n = 5), the mean serum drug concentration at 1 h after treatment was 112.1 +/- 40.3 ng/mL. By 24 h after treatment, the concentration had fallen to 13.0 +/- 3.3 ng/mL. Thereafter, the serum drug concentration-versus-time profile and the pharmacokinetic parameters obtained following non-compartmental analysis were similar to those obtained following intramuscular treatment of Friesian steers.     

Pharmacokinetics of norfloxacin in dogs after single intravenous and single and multiple oral administrations of the drug

Norfloxacin was given to 6 healthy dogs at a dosage of 5 mg/kg of body weight IV and orally in a complete crossover study, and orally at dosages of 5, 10, and 20 mg/kg to 6 healthy dogs in a 3-way crossover study. For 24 hours, serum concentration was monitored serially after each administration. Another 6 dogs were given 5 mg of norfloxacin/kg orally every 12 hours for 14 days, and serum concentration was determined serially for 12 hours after the first and last administration of the drug. Complete blood count and serum biochemical analysis were performed before and after 14 days of oral norfloxacin administration, and clinical signs of drug toxicosis were monitored twice daily during norfloxacin administration. Urine concentration of norfloxacin was determined periodically during serum acquisition periods. Norfloxacin concentration was determined, using high-performance liquid chromatography with a limit of detection of 25 ng of norfloxacin/ml of serum or urine. Serum norfloxacin pharmacokinetic values after single IV dosing in dogs were best modeled, using a 2-compartment open model, with distribution and elimination half-lives of 0.467 and 3.56 hours (harmonic means), respectively. Area-derived volume of distribution (Vd area) was 1.77 +/- 0.69 L/kg (arithmetic mean +/- SD), and serum clearance (Cls) was 0.332 +/- 0.115 L/h/kg. Mean residence time was 4.32 +/- 0.98 hour. Comparison of the area under the curve (AUC; derived, using model-independent calculations) after iv administration (5 mg/kg) with AUC after oral administration (5 mg/kg) in the same dogs indicated bioavailability of 35.0 +/- 46.1%, with a mean residence time after oral administration of 5.71 +/-2.24 hours. Urine concentration was 33.8 +/- 15.3 micrograms/ml at 4 hours after a single dose of 5 mg/kg given orally, whereas concentration after 20 mg/kg was given orally was 56.8 +/- 18.0 micrograms/ml at 6 hours after dosing. Twelve hours after drug administration, urine concentration was 47.4 +/- 20.6 micrograms/ml after the 5-mg/kg dose and 80.6 +/- 37.7 micrograms/ml after the 20/mg/kg dose.(ABSTRACT TRUNCATED AT 250 WORDS)     

Single-dose pharmacokinetics of detomidine in the horse and cow

The pharmacokinetics of detomidine, a novel analgesic sedative, was studied in the major target species after high (80 micrograms/kg) i.v. and i.m. doses. In addition, drug residues in some organs were determined. Concentrations were measured using a sensitive, detomidine-specific radio-immunoassay method. Rapid absorption following i.m. dosing occurred. Absorption half-lives were 0.15 h (horse) and 0.08 h (cattle). The mean peak concentration in the horse (51.3 ng/ml) was achieved in 0.5 h and in the cow (65.8 ng/ml) in 0.26 h. The areas under the concentration curve after i.m. dosing were 66% (horse) and 85% (cow) of the corresponding i.v. values. Distribution was rapid with half-lives of 0.15 h (horse, i.v.) and 0.24 h (cow, i.v.). The apparent volume of distribution was higher after the i.m. dosing (horse 1.56 l/kg, cow 1.89 l/kg) than after i.v. dosing (horse 0.74 l/kg, cow 0.73 l/kg). Elimination half-lives were 1.19 h (horse) and 1.32 h (cow) for the i.v. dose and 1.78 h (horse) and 2.56 h (cow) for the i.m. dose. Total clearances ranged from 6.7 (horse, i.v.) to 12.3 (cow, i.m.) ml/min/kg. Renal clearances were less than 1% of the total clearances showing negligible excretion of the drug in urine and suggesting elimination by metabolism. A cross-reacting metabolite in urine corresponded to less than 1.5% of the detomidine dose's immunoreactivity. High-dose detomidine increased urine flow significantly. Excretion of detomidine in milk in cattle was extremely low. No detectable amounts were present 23 h after dosing.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of cefotaxime in the dog

Each of five dogs was given cefotaxime at a dose rate of 50 mg/kg by intravenous, intramuscular and subcutaneous routes, in three separate treatments. Plasma concentration time profiles were characterised by a linear two-compartment model after the intravenous administration. After intravenous, intramuscular and subcutaneous injections the mean biological half-lives were 0.74, 0.83 and 1.71 hours, respectively. The apparent steady state volume of distribution was 0.48 litre/kg and body clearance after intravenous injection was approximately 0.63 litre/hour/kg. After intramuscular and subcutaneous injections peak plasma cefotaxime concentrations were 47 +/- 15 and 29.6 +/- 16 micrograms/ml at 0.5 and 0.8 hours, respectively. The average bioavailability of cefotaxime given by intramuscular injection was 86.5 per cent and for cefotaxime given subcutaneously it was approximately 100 per cent. After two hours, the cefotaxime plasma concentration remained higher after subcutaneous than after intramuscular administration.     

Some pharmacokinetic parameters of ampicillin/sulbactam combination after intravenous and intramuscular administration to goats

Summary

Some pharmacokinetic parameters of an ampicillin/sulbactam (2:1) combination were studied in six goats, after intravenous and intramuscular injection at a single dosage of 20 mg/kg bodyweight (13.33 mg/kg of sodium ampicillin and 6.67 mg/kg of sodium sulbactam). The drugs were distributed according to an open two‐compartment model. The apparent volumes of distribution calculated by the area method of ampicillin and sulbactam were 0.34 ± 0.04 l/kg and 0.45 ± 0.15 1/kg, respectively, and the total body clearances were 0.72 ± 0.11 and 0.38 ± 0.07 l/kg.h. The half‐lives of ampicillin after intravenous and intramuscular administration were 0.32 ± 0.04 h and 0.71 ± 0.14 h, respectively. For sulbactam the half‐lives were 0.79 ± 0.18 h and 1.13 ± 0.21 h after administration by the same routes. The bioavailability after intramuscular injection was high and similar for both drugs (98,29% for ampicillin and 101.84% for sulbactam). The mean peak plasma levels of ampicillin (0.43 ± 0.27 h) and sulbactam (0.34 ± 0.14 h) were reached at a similar time, and peak concentrations were also similar and non‐proportional to the dose of the products administered (11.02 ± 3.11 mg/l of ampicillin and 9.5 ± 0.98 mg/l of sulbactam).